Reducing Gastrointestinal Bleeding With Proton Pump Inhibitor Therapy in Acute Venous Thromboembolism

Venous Thromboembolism Clinical Trial

Official title:

Reducing Gastrointestinal Bleeding With Proton Pump Inhibitor Therapy in Acute Venous Thromboembolism: Pilot Randomized Study (RADIANT Study)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06393868
• Other study ID #: RADIANT-001
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: September 2024

Study information

• Verified date: April 2024
• Source: Ottawa Hospital Research Institute
• Contact: Deborah Siegal, MD
• Phone: (613) 737-8899
• Email: dsiegal[@]toh.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators are studying whether treatment with a proton pump inhibitor called omeprazole reduces gastrointestinal bleeding in older adults taking blood thinners for a blood clot (venous thromboembolism). The purpose of this study, a pilot study or a feasibility study, is to test the study plan and determine whether enough participants will join a larger study and accept the study procedures.

Description:

Venous thromboembolism (VTE) refers to blood clots that form in the veins of the body, including the arms or legs (deep vein thrombosis [DVT]), abdomen (portal vein thrombosis), or lungs (pulmonary embolism [PE]). These blood clots are treated with medication to reduce blood clotting called anticoagulants. The main complication of anticoagulants is bleeding, the majority of which comes from the stomach or intestines (gastrointestinal tract). Anticoagulants do not cause bleeding, but they may make bleeding worse. Uncommonly, serious gastrointestinal (GI) bleeding can happen leading to hospitalization and even death. The chance of bleeding is highest in the first few months after starting anticoagulants.

Proton pump inhibitors (PPIs) are medications that lower the acid content of the stomach. The medication in this study, a type of proton pump inhibitor called omeprazole, is approved in Canada for treating stomach ulcers, heartburn, and a stomach infection called Helicobacter pylori. The use of omeprazole in this study is considered investigational. This means that Health Canada has not approved the use of omeprazole as a treatment for preventing gastrointestinal bleeding in patients taking anticoagulants. Some studies suggest that they may reduce gastrointestinal bleeding for people taking anticoagulants.

The investigators are studying whether treatment with a proton pump inhibitor called omeprazole reduces gastrointestinal bleeding in older adults taking anticoagulants for venous thromboembolism.

The investigators plan to do a large, randomized trial which is the best way to test the effect of a treatment. To do this, some of the participants in this study will get omeprazole and others will get a placebo (a substance that looks like the study omeprazole but does not have any active or medicinal ingredients). The placebo in this study is not intended to have any effect on bleeding. A placebo is used to make the results of the study more reliable.

Primary Objective To assess the feasibility of a full-scale double-blind placebo-controlled randomized trial to determine whether omeprazole reduces the risk of upper GI bleeding in older adults receiving anticoagulation for acute VTE compared to placebo.

Secondary Objectives:

1. To measure additional feasibility outcomes

2. To measure informative outcomes

3. To measure key clinical outcomes

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 360
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

1. Male or female 65 years or older at the time of enrolment. Enrolment is limited to older adults as age is an important non-modifiable risk factor for bleeding. This will ensure the study population includes participants who may be more likely to benefit from omeprazole (compared to those with no risk factors) because all participants will have at least 1 risk factor for bleeding.

2. Acute VTE diagnosed within the previous 7 days which includes VTE at any site such as (but not limited to) DVT of upper or lower limbs, PE, cerebral vein thrombosis, portal vein thrombosis, other splanchnic vein thrombosis.

3. Planned for 3 months (90 days) or more of therapeutic anticoagulation with any anticoagulant.

4. Patient or delegate is able and willing to comply with follow-up examinations contained within the consent form.

Exclusion Criteria:

1. Currently prescribed PPI for regular daily use (patients receiving H2 receptor antagonists will not be excluded),

2. previous upper GI bleeding,

3. need for dual antiplatelet therapy,

4. contraindications to omeprazole (hypersensitivity to omeprazole, or other substituted benzimidazole PPIs, concomitant use with products that contain rilpivirine, up to the discretion of the site investigator),

5. life expectancy is less than 3 months.

Related Conditions & MeSH terms

• Blood Clot
• Gastro Intestinal Bleeding
• Gastrointestinal Hemorrhage
• Hemorrhage
• Thromboembolism
• Thrombosis
• Venous Thromboembolism

Intervention

Drug:
• Omeprazole 20 mg Oral Tablet
Omeprazole once daily for 90 days

Other:
• Placebo
Placebo once daily for 90 days

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Deborah Siegal

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Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Risk Factors	The proportion of participants with the following risk factors for bleeding at baseline: decreased kidney function (defined as estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2), active cancer, concurrent antiplatelet and/or NSAID therapy, chronic liver disease, chronic anemia.	24 months
Other	Patients already prescribed proton pump inhibitor	The proportion of screened patients already receiving prescribed proton pump inhibitor therapy	24 months
Other	Reasons for Declining Participation	Patients are not required to provide a reason for declining to participate. However, for those patients who are willing to share, reasons for declining participation will be reviewed	24 months
Other	New PPI prescription	The proportion of participants with new prescription for proton pump inhibitor during the study	27 months
Other	Recurrent VTE	The proportion of patients that have a recurrent venous thromboembolism during the study	27 months
Other	Mortality	The proportion of patients who die from gastrointestinal bleeding, and all-cause mortality during the study	27 months
Other	Serious Adverse Events	The proportion of patients who have a serious adverse event during the study	27 months
Other	Change in health-related quality of life	Change in health-related quality of life as measured by the EuroQol EQ-5D-5L Quality of Life questionnaire at 90 days compared to baseline. This questionnaire includes the patient's thoughts about their health, including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. The lowest possible score is 5 and the highest is 25. A lower score represents a worse quality of life. The questionnaire also includes a Visible Analog Scale where patients are asked to picture a vertical line that is numbered from 0 to 100. 100 at the top of the line means the best health the patient can imagine and 0 at the bottom of the line means the worst health the patient can imagine. Patients are asked to provide a number that best represents their health at the time of completing the questionnaire.	27 months
Other	Change in functional status	Change in functional status as measured by the Standard Assessment of Global Activities in the Elderly (SAGE) scale at 90 days compared to baseline. The SAGE questionnaire measures what patients are doing in their community and their homes. Patients are asked to indicate the level of difficulty they have with each of the questions in the past month with a response of no difficulty, mild, moderate, or severe difficulty. Mild = minimal/occasional difficulty that does not affect the ability to perform the activity or task; Moderate = some/regular difficulty that does affect the ability to perform the task, although they may still be able to perform the task; Severe = extreme/constant difficulty performing the task or the task is not completed and/or is completed by someone else because of its difficulty.	27 months
Other	Clinically Relevant Upper Gastrointestinal Bleeding Events	Adjudicated clinically relevant upper gastrointestinal bleeding (major upper gastrointestinal bleeding plus clinically relevant non-major [CRNM] upper GI bleeding, adapted from International Society on Thrombosis and Haemostasis (ISTH) criteria for major bleeding and CRNM bleeding).	27 months
Other	Rate of endoscopically confirmed upper gastrointestinal bleeding	Proportion of patients who have upper gastrointestinal bleeding as confirmed by endoscope at 30, 60, and 90 days post randomization	27 months
Other	Rate of lower gastrointestinal bleeding	Proportion of patients who have lower gastrointestinal bleeding at 30, 60, and 90 days post randomization	27 months
Other	All major gastrointestinal bleeding	Proportion of patients who have confirmed major gastrointestinal bleeding by adjudication at 30, 60, and 90 days post randomization	27 months
Other	All clinically relevant non-major gastrointestinal bleeding	Proportion of patients who have confirmed clinically relevant non-major gastrointestinal bleeding by adjudication at 30, 60. 90 days	27 months
Other	All major bleeding	Proportion of patients who have confirmed major bleeding by adjudication, including major GI bleeding) at 30, 60, 90 days post randomization	27 months
Other	All clinically relevant non-major bleeding	Proportion of patients who have confirmed clinically relevant non-major bleeding (including CRNM GI bleeding) at 30, 60, and 90 days post randomization	27 months
Other	Hospitalization for gastrointestinal bleeding	Proportion of patients hospitalized for gastrointestinal bleeding at 30, 60. and 90 days post randomization	27 months
Primary	Study feasibility at participating centres	The mean number of participants recruited per site per month	24 months
Secondary	Eligibility Rate	Proportion of screened patients who are eligible	24 months
Secondary	Consent Rate	Proportion of eligible patients who provide consent	24 months
Secondary	Retention Rate	Proportion of participants who completed all study procedures	27 months
Secondary	Adherence Rate	adherence to study drug measured by pill count or assessing the patient diary at the end of follow-up	27 months